ID   DUS8_HUMAN              Reviewed;         625 AA.
AC   Q13202; Q86SS8;
DT   15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT   10-FEB-2009, sequence version 2.
DT   12-OCT-2022, entry version 175.
DE   RecName: Full=Dual specificity protein phosphatase 8;
DE            EC=3.1.3.16;
DE            EC=3.1.3.48;
DE   AltName: Full=Dual specificity protein phosphatase hVH-5;
GN   Name=DUSP8; Synonyms=C11orf81, VH5;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC   TISSUE=Fetal brain;
RX   PubMed=7561881; DOI=10.1046/j.1471-4159.1995.65041823.x;
RA   Martell K.J., Seasholtz A.F., Kwak S.P., Clemens K.K., Dixon J.E.;
RT   "hVH-5: a protein tyrosine phosphatase abundant in brain that inactivates
RT   mitogen-activated protein kinase.";
RL   J. Neurochem. 65:1823-1833(1995).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16554811; DOI=10.1038/nature04632;
RA   Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA   Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA   Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA   Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA   Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA   Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT   "Human chromosome 11 DNA sequence and analysis including novel gene
RT   identification.";
RL   Nature 440:497-500(2006).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain, and Skin;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [4] {ECO:0007744|PDB:4JMK}
RP   X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 160-310, AND SUBUNIT.
RX   PubMed=24531476; DOI=10.1107/s1399004713029866;
RA   Jeong D.G., Wei C.H., Ku B., Jeon T.J., Chien P.N., Kim J.K., Park S.Y.,
RA   Hwang H.S., Ryu S.Y., Park H., Kim D.S., Kim S.J., Ryu S.E.;
RT   "The family-wide structure and function of human dual-specificity protein
RT   phosphatases.";
RL   Acta Crystallogr. D 70:421-435(2014).
CC   -!- FUNCTION: Has phosphatase activity with synthetic phosphatase
CC       substrates and negatively regulates mitogen-activated protein kinase
CC       activity, presumably by catalysing their dephosphorylation. Expected to
CC       display protein phosphatase activity toward phosphotyrosine,
CC       phosphoserine and phosphothreonine residues.
CC       {ECO:0000250|UniProtKB:O09112}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H2O + O-phospho-L-tyrosyl-[protein] = L-tyrosyl-[protein] +
CC         phosphate; Xref=Rhea:RHEA:10684, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC         COMP:10137, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:46858,
CC         ChEBI:CHEBI:82620; EC=3.1.3.48; Evidence={ECO:0000255|PROSITE-
CC         ProRule:PRU10044};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H2O + O-phospho-L-seryl-[protein] = L-seryl-[protein] +
CC         phosphate; Xref=Rhea:RHEA:20629, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC         COMP:11604, ChEBI:CHEBI:15377, ChEBI:CHEBI:29999, ChEBI:CHEBI:43474,
CC         ChEBI:CHEBI:83421; EC=3.1.3.16;
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H2O + O-phospho-L-threonyl-[protein] = L-threonyl-[protein] +
CC         phosphate; Xref=Rhea:RHEA:47004, Rhea:RHEA-COMP:11060, Rhea:RHEA-
CC         COMP:11605, ChEBI:CHEBI:15377, ChEBI:CHEBI:30013, ChEBI:CHEBI:43474,
CC         ChEBI:CHEBI:61977; EC=3.1.3.16;
CC   -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:24531476}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:O09112}. Nucleus
CC       {ECO:0000250|UniProtKB:O09112}.
CC   -!- TISSUE SPECIFICITY: Abundant in brain, heart and skeletal muscle.
CC       {ECO:0000269|PubMed:7561881}.
CC   -!- SIMILARITY: Belongs to the protein-tyrosine phosphatase family. Non-
CC       receptor class dual specificity subfamily. {ECO:0000305}.
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DR   EMBL; U27193; AAA83151.1; -; mRNA.
DR   EMBL; AP006285; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC038231; AAH38231.1; -; mRNA.
DR   EMBL; BC045110; AAH45110.1; -; mRNA.
DR   CCDS; CCDS7724.1; -.
DR   RefSeq; NP_004411.2; NM_004420.2.
DR   RefSeq; XP_011518234.1; XM_011519932.2.
DR   RefSeq; XP_011518235.1; XM_011519933.2.
DR   PDB; 4JMK; X-ray; 1.90 A; A/B=160-310.
DR   PDBsum; 4JMK; -.
DR   AlphaFoldDB; Q13202; -.
DR   SMR; Q13202; -.
DR   BioGRID; 108183; 40.
DR   IntAct; Q13202; 3.
DR   MINT; Q13202; -.
DR   STRING; 9606.ENSP00000380530; -.
DR   DEPOD; DUSP8; -.
DR   iPTMnet; Q13202; -.
DR   PhosphoSitePlus; Q13202; -.
DR   BioMuta; DUSP8; -.
DR   DMDM; 223590200; -.
DR   jPOST; Q13202; -.
DR   MassIVE; Q13202; -.
DR   MaxQB; Q13202; -.
DR   PaxDb; Q13202; -.
DR   PeptideAtlas; Q13202; -.
DR   PRIDE; Q13202; -.
DR   ProteomicsDB; 59222; -.
DR   Antibodypedia; 10181; 213 antibodies from 30 providers.
DR   DNASU; 1850; -.
DR   Ensembl; ENST00000331588.4; ENSP00000329539.4; ENSG00000184545.11.
DR   Ensembl; ENST00000397374.8; ENSP00000380530.3; ENSG00000184545.11.
DR   Ensembl; ENST00000610856.1; ENSP00000479946.1; ENSG00000278165.3.
DR   Ensembl; ENST00000617829.1; ENSP00000481775.1; ENSG00000273793.3.
DR   Ensembl; ENST00000625578.2; ENSP00000487017.1; ENSG00000273793.3.
DR   Ensembl; ENST00000629053.2; ENSP00000487093.1; ENSG00000278165.3.
DR   GeneID; 1850; -.
DR   KEGG; hsa:1850; -.
DR   MANE-Select; ENST00000397374.8; ENSP00000380530.3; NM_004420.3; NP_004411.2.
DR   UCSC; uc001lts.3; human.
DR   CTD; 1850; -.
DR   DisGeNET; 1850; -.
DR   GeneCards; DUSP8; -.
DR   HGNC; HGNC:3074; DUSP8.
DR   HPA; ENSG00000184545; Tissue enhanced (pituitary).
DR   MIM; 602038; gene.
DR   neXtProt; NX_Q13202; -.
DR   OpenTargets; ENSG00000184545; -.
DR   PharmGKB; PA27531; -.
DR   VEuPathDB; HostDB:ENSG00000184545; -.
DR   eggNOG; KOG1716; Eukaryota.
DR   GeneTree; ENSGT00940000160004; -.
DR   HOGENOM; CLU_027074_16_0_1; -.
DR   InParanoid; Q13202; -.
DR   OMA; ICESHFM; -.
DR   OrthoDB; 1576308at2759; -.
DR   PhylomeDB; Q13202; -.
DR   TreeFam; TF105122; -.
DR   PathwayCommons; Q13202; -.
DR   Reactome; R-HSA-112409; RAF-independent MAPK1/3 activation.
DR   Reactome; R-HSA-5675221; Negative regulation of MAPK pathway.
DR   Reactome; R-HSA-9652817; Signaling by MAPK mutants.
DR   SignaLink; Q13202; -.
DR   SIGNOR; Q13202; -.
DR   BioGRID-ORCS; 1850; 15 hits in 1080 CRISPR screens.
DR   ChiTaRS; DUSP8; human.
DR   GenomeRNAi; 1850; -.
DR   Pharos; Q13202; Tbio.
DR   PRO; PR:Q13202; -.
DR   Proteomes; UP000005640; Chromosome 11.
DR   RNAct; Q13202; protein.
DR   Bgee; ENSG00000184545; Expressed in mucosa of stomach and 96 other tissues.
DR   Genevisible; Q13202; HS.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR   GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR   GO; GO:0017017; F:MAP kinase tyrosine/serine/threonine phosphatase activity; IBA:GO_Central.
DR   GO; GO:0017018; F:myosin phosphatase activity; IEA:UniProtKB-EC.
DR   GO; GO:0016791; F:phosphatase activity; ISS:UniProtKB.
DR   GO; GO:0004721; F:phosphoprotein phosphatase activity; IBA:GO_Central.
DR   GO; GO:0004725; F:protein tyrosine phosphatase activity; IEA:UniProtKB-EC.
DR   GO; GO:0008330; F:protein tyrosine/threonine phosphatase activity; IBA:GO_Central.
DR   GO; GO:0016311; P:dephosphorylation; ISS:UniProtKB.
DR   GO; GO:0043409; P:negative regulation of MAPK cascade; IBA:GO_Central.
DR   GO; GO:0006470; P:protein dephosphorylation; IEA:InterPro.
DR   Gene3D; 3.40.250.10; -; 1.
DR   Gene3D; 3.90.190.10; -; 1.
DR   InterPro; IPR000340; Dual-sp_phosphatase_cat-dom.
DR   InterPro; IPR008343; MKP.
DR   InterPro; IPR029021; Prot-tyrosine_phosphatase-like.
DR   InterPro; IPR001763; Rhodanese-like_dom.
DR   InterPro; IPR036873; Rhodanese-like_dom_sf.
DR   InterPro; IPR016130; Tyr_Pase_AS.
DR   InterPro; IPR000387; Tyr_Pase_dom.
DR   InterPro; IPR020422; TYR_PHOSPHATASE_DUAL_dom.
DR   Pfam; PF00782; DSPc; 1.
DR   Pfam; PF00581; Rhodanese; 1.
DR   PRINTS; PR01764; MAPKPHPHTASE.
DR   SMART; SM00195; DSPc; 1.
DR   SMART; SM00450; RHOD; 1.
DR   SUPFAM; SSF52799; SSF52799; 1.
DR   SUPFAM; SSF52821; SSF52821; 1.
DR   PROSITE; PS50206; RHODANESE_3; 1.
DR   PROSITE; PS00383; TYR_PHOSPHATASE_1; 1.
DR   PROSITE; PS50056; TYR_PHOSPHATASE_2; 1.
DR   PROSITE; PS50054; TYR_PHOSPHATASE_DUAL; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Cytoplasm; Hydrolase; Nucleus; Protein phosphatase;
KW   Reference proteome.
FT   CHAIN           1..625
FT                   /note="Dual specificity protein phosphatase 8"
FT                   /id="PRO_0000094810"
FT   DOMAIN          23..138
FT                   /note="Rhodanese"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00173"
FT   DOMAIN          160..302
FT                   /note="Tyrosine-protein phosphatase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00160"
FT   REGION          306..586
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        313..335
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        498..522
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        556..586
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        246
FT                   /note="Phosphocysteine intermediate"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00160"
FT   CONFLICT        299
FT                   /note="S -> T (in Ref. 1; AAA83151)"
FT                   /evidence="ECO:0000305"
FT   STRAND          162..165
FT                   /evidence="ECO:0007829|PDB:4JMK"
FT   STRAND          168..171
FT                   /evidence="ECO:0007829|PDB:4JMK"
FT   HELIX           173..176
FT                   /evidence="ECO:0007829|PDB:4JMK"
FT   HELIX           179..184
FT                   /evidence="ECO:0007829|PDB:4JMK"
FT   STRAND          187..192
FT                   /evidence="ECO:0007829|PDB:4JMK"
FT   STRAND          195..197
FT                   /evidence="ECO:0007829|PDB:4JMK"
FT   HELIX           205..207
FT                   /evidence="ECO:0007829|PDB:4JMK"
FT   STRAND          208..210
FT                   /evidence="ECO:0007829|PDB:4JMK"
FT   STRAND          215..218
FT                   /evidence="ECO:0007829|PDB:4JMK"
FT   HELIX           222..224
FT                   /evidence="ECO:0007829|PDB:4JMK"
FT   HELIX           225..237
FT                   /evidence="ECO:0007829|PDB:4JMK"
FT   STRAND          241..245
FT                   /evidence="ECO:0007829|PDB:4JMK"
FT   STRAND          247..251
FT                   /evidence="ECO:0007829|PDB:4JMK"
FT   HELIX           252..265
FT                   /evidence="ECO:0007829|PDB:4JMK"
FT   HELIX           269..279
FT                   /evidence="ECO:0007829|PDB:4JMK"
FT   HELIX           287..306
FT                   /evidence="ECO:0007829|PDB:4JMK"
SQ   SEQUENCE   625 AA;  65827 MW;  C7C808407B724FFC CRC64;
     MAGDRLPRKV MDAKKLASLL RGGPGGPLVI DSRSFVEYNS WHVLSSVNIC CSKLVKRRLQ
     QGKVTIAELI QPAARSQVEA TEPQDVVVYD QSTRDASVLA ADSFLSILLS KLDGCFDSVA
     ILTGGFATFS SCFPGLCEGK PAALLPMSLS QPCLPVPSVG LTRILPHLYL GSQKDVLNKD
     LMTQNGISYV LNASNSCPKP DFICESRFMR VPINDNYCEK LLPWLDKSIE FIDKAKLSSC
     QVIVHCLAGI SRSATIAIAY IMKTMGMSSD DAYRFVKDRR PSISPNFNFL GQLLEYERSL
     KLLAALQGDP GTPSGTPEPP PSPAAGAPLP RLPPPTSESA ATGNAAAREG GLSAGGEPPA
     PPTPPATSAL QQGLRGLHLS SDRLQDTNRL KRSFSLDIKS AYAPSRRPDG PGPPDPGEAP
     KLCKLDSPSG AALGLSSPSP DSPDAAPEAR PRPRRRPRPP AGSPARSPAH SLGLNFGDAA
     RQTPRHGLSA LSAPGLPGPG QPAGPGAWAP PLDSPGTPSP DGPWCFSPEG AQGAGGVLFA
     PFGRAGAPGP GGGSDLRRRE AARAEPRDAR TGWPEEPAPE TQFKRRSCQM EFEEGMVEGR
     ARGEELAALG KQASFSGSVE VIEVS
//